Background : Rivers are a fraction of flowing waters in the worlds and one of the important sources of water for different consumptions such as agricultural, drinking and industrial uses. The aim of this study was to assess water quality of the Khorramrood River in Khorramabad by NSFWQI index. Materials and Methods: In this cross-sectional study, quality parameters needed for NASWQI index calculation such as BOD5, dissolved oxygen (DO), total nitrate, fecal coliform, pH, total phosphate, temperature, turbidity and total suspended solids content were measured for six months (from July to December 2012)using standard methods at six selected stations. The river zoning conducted by GIS software. Results: According to the results obtained through this study, the highest and the lowest water quality value was observed in stations 1 and 6 with NSFWQI indexes 82 water with good quality, 42 water with bad quality, respectively. With moving toward last station (from 1 to 6 station) water pollution increased. Conclusion: Results of the study indicated that water quality index NSFWQI is a good index to identify the effect of polluter sources on the river water. Based on the average of the index NSFWQI, water quality in station one was good, in the second, third and fourth stations were mediocre and the fifth and sixth stations had bad quality. These results allow to make decisions about monitoring and controlling water pollution sources, as well as provide different efficient uses of it by relevant authorities.